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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Septic shock is a highly lethal condition where several pathogenic factors are involved in progressive tissue hypoperfusion&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> Fluid resuscitation is a first-line therapy to reverse hypoperfusion&#46; However&#44; this may induce fluid overload&#44; particularly when administered to fluid-unresponsive patients or when inappropriate resuscitation goals are pursued&#46; Unfortunately&#44; despite extensive research&#44; many uncertainties remain on the best perfusion monitoring and resuscitation target&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">The complexities of persistent hyperlactatemia</span><p id="par0010" class="elsevierStylePara elsevierViewall">Recent guidelines recommend lactate normalization as a resuscitation target&#46; However&#44; the rationale of lactate-guided therapy has been challenged as it may expose patients to the risk of over-resuscitation considering that the decrease in lactate levels over time is relatively slow even in survivors&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">2&#44;3</span></a> In addition&#44; lactate is a non-specific marker of hypoperfusion and several pathogenic mechanisms besides hypoperfusion may be involved&#46; Adrenergic-driven muscle glycolysis and impaired hepatic lactate clearance are important confounding mechanisms in septic shock&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#44;2</span></a> Recognizing a clinical pattern of hypoperfusion-related hyperlactatemia is important since optimizing systemic blood flow in that context could improve prognosis&#46; In contrast&#44; pursuing additional resuscitation in non-hypoperfusion-related cases might lead to the toxicity of over-resuscitation&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Multimodal perfusion monitoring including flow-sensitive parameters such as central venous O<span class="elsevierStyleInf">2</span> saturation &#40;ScvO<span class="elsevierStyleInf">2</span>&#41;&#44; central venous-arterial pCO<span class="elsevierStyleInf">2</span> gradient &#40;Pcv-aCO<span class="elsevierStyleInf">2</span>&#41;&#44; and peripheral perfusion&#44; may disclose the presence of hypoperfusion-related hyperlactatemia when any of these variables is abnormal&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#44;2&#44;4</span></a> Persistent hyperlactatemia without a hypoperfusion context is associated with a better prognosis&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> and eventually this condition could be managed more conservatively&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">The role of capillary refill time &#40;CRT&#41; assessment</span><p id="par0020" class="elsevierStylePara elsevierViewall">CRT emerges as a rational alternative to guide septic shock resuscitation&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> The skin territory lacks auto-regulatory flow control&#44; and therefore&#44; sympathetic activation impairs skin perfusion during circulatory dysfunction&#44; a phenomenon that can be evaluated by peripheral perfusion assessment&#46; Several studies confirm that abnormal peripheral perfusion after initial<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> or advanced<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> resuscitation is associated with increased morbidity and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">6&#44;7</span></a> The improved prognosis associated with CRT normalization&#44; its rapid-response time to fluid loading&#44; its relative simplicity&#44; its availability in resource-limited settings&#44; and its capacity to change in parallel with perfusion of physiologically relevant territories such as the hepatosplanchnic region&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> constitute strong reasons to consider CRT as target for initial septic shock resuscitation&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">The ANDROMEDA-SHOCK trial</span><p id="par0025" class="elsevierStylePara elsevierViewall">ANDROMEDA-SHOCK was a multicenter&#44; randomized controlled trial comparing CRT- versus lactate-targeted resuscitation in patients with early septic shock&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> The hypothesis was that targeting CRT assessed with a standardized method&#44; would lead to decreased mortality and organ dysfunction&#46; The protocol mandated sequential steps starting with fluid challenges&#44; followed by vasoactive-related interventions if necessary&#44; until the target was reached&#46; CRT-targeted resuscitation was associated with lower mortality &#40;34&#46;9&#37; vs&#46; 43&#46;4&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;06&#41;&#44; beneficial effects on organ dysfunction&#44; and less treatment intensity&#46; The worldwide impact and immediate application of CRT-guided resuscitation makes additional research an urgent task &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">The concept of hemodynamic coherence in septic shock</span><p id="par0030" class="elsevierStylePara elsevierViewall">Hemodynamic coherence is a condition in which resuscitation of systemic macrohemodynamic variables results in concurrent improvement in regional and microcirculatory blood flow&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">9&#8211;11</span></a>&#46; Impaired vascular tone with decreased venous return and arterial hypotension are key pathogenic mechanisms in early septic shock&#46; At this stage&#44; fluid resuscitation &#40;in fluid-responsive patients&#41; and mean arterial pressure &#40;MAP&#41; optimization may improve macrocirculatory&#44; regional&#44; and microcirculatory blood flow&#44; which is consistent with preserved hemodynamic coherence and associated with better prognosis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">At more advanced stages&#44; when excessive adrenergic tone and microvascular&#47;endothelial inflammation predominate&#44; regional flow distribution and microcirculatory dysfunction may not respond to systemic blood flow optimization&#46; Thus&#44; hemodynamic coherence is lost&#44; and efforts to further increase stroke volume or MAP by fluids or vasoactive agents might lead to fluid overload or catecholamine toxicity&#46; This could result in worsening tissue perfusion by promoting interstitial edema&#44; or by further deteriorating regional perfusion&#46; How to treat patients at this stage is uncertain and a matter of future research&#44; including the potential role of early immunomodulating therapies&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">CRT&#58; the link between macrocirculation and the microcirculation&#63;</span><p id="par0040" class="elsevierStylePara elsevierViewall">Capillary refill time &#40;CRT&#41; appears as a physiologically sound target and its improvement after stroke volume optimization is a signal of tissue reperfusion in patients with septic shock&#46; Some observations support the potential role of CRT in revealing the status of hemodynamic coherence&#46; First&#44; three recent studies show that patients with normal vs&#46; abnormal CRT after fluid resuscitation exhibit a highly significant difference in mortality &#40;ranging from 9 to 23&#37; vs&#46; 45 to 55&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">5&#8211;7</span></a> This remarkable and consistent difference suggests&#44; although does not prove&#44; a preserved hemodynamic coherence in CRT normalizers &#40;responders&#41;&#46; Second&#44; improvement in CRT after fluid resuscitation is associated with a parallel increase in hepatosplanchnic blood flow&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> Third&#44; CRT showed the fastest kinetics of recovery in septic shock survivors as compared with other commonly used perfusion parameters&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Fourth&#44; normalization of CRT in the ANDROMEDA-shock study was associated with less organ dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">On the other hand&#44; an abnormal CRT not responding to increments in systemic flow might be explained by several mechanisms including a more advanced stage of septic shock with uncoupling or loss of hemodynamic coherence&#59; an excessive adrenergic tone with regional hypoperfusion&#59; or a more severe systemic inflammatory state with endothelial&#47;coagulation activation&#47;dysfunction which could lead to impairment and heterogeneity of microcirculatory flow&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> None of these mechanisms may respond to systemic flow optimization at this stage&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Based on the preceding considerations&#44; we could propose that CRT response to a rapid flow increasing maneuver may be used as a novel &#8220;hemodynamic coherence test&#46;&#8221; A parallel improvement in regional blood flow&#44; microcirculation and hypoperfusion-related parameters should be expected in patients that normalize CRT&#44; as reflection of preserved hemodynamic coherence&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusions</span><p id="par0055" class="elsevierStylePara elsevierViewall">Multimodal perfusion monitoring might be useful to determine a hypoperfusion-context in persistent hyperlactatemia&#44; thus promoting a physiologically-oriented septic shock resuscitation&#46; CRT-guided septic shock resuscitation is associated with decreased mortality and organ dysfunction&#46; CRT changes after rapid flow increasing maneuvers may identify the status of hemodynamic coherence&#44; helping clinicians to decide on the most appropriate strategy for each stage&#46; Further research is required to test these hypotheses&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflict of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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                  \t\t\t\t"><span class="elsevierStyleItalic">Main findings of the ANDROMEDA-SHOCK study favoring CRT-targeted septic shock resuscitation</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lower mortality &#40;34&#46;9&#37; vs&#46; 43&#46;4&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;06&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Less organ dysfunctions at 72<span class="elsevierStyleHsp" style=""></span>h &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;045&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lower mortality in the predefined subgroup of patients with less organ dysfunctions at baseline &#40;20&#46;4&#37; vs&#46; 39&#46;3&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Faster improvement in organ dysfunctions during the first 72<span class="elsevierStyleHsp" style=""></span>h &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Less resuscitation fluids &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Some unsolved issues and challenges for a CRT-focused research agenda</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mechanisms of the beneficial effect of CRT-targeted resuscitation in the ANDROMEDA-SHOCK study&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pathophysiologic determinants of an abnormal CRT&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Does CRT accurately represent skin blood flow&#63;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Is CRT an equivalent of a vascular occlusion test to detect abnormal microvascular reactivity&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Is there a relationship between an abnormal CRT and adrenergic tone&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Does CRT respond in real-time to increments in systemic blood flow&#63;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>What is the impact of vasoactive agents on CRT&#63;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Does normalization of CRT after a fluid challenge predict the status of hemodynamic coherence between macrocirculation and regional&#47;microcirculatory blood flow&#63;&nbsp;\t\t\t\t\t\t\n
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Perspectives on perfusion monitoring in septic shock after the ANDROMEDA-SHOCK trial
Perspectivas sobre la monitorización de la perfusión en el choque séptico tras el ensayo ANDROMEDA-SHOCK
G. Hernándeza,
Corresponding author
glennguru@gmail.com

Corresponding author.
, J. Bakkera,b,c,d
a Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
b Department of Pulmonology and Critical Care, Columbia University Medical Center, New York, USA
c Department of Pulmonology and Critical Care, NYU Medical Center, Bellevue Hospital, New York, USA
d Erasmus MC University Medical Center, Rotterdam, The Netherlands
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Septic shock is a highly lethal condition where several pathogenic factors are involved in progressive tissue hypoperfusion&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> Fluid resuscitation is a first-line therapy to reverse hypoperfusion&#46; However&#44; this may induce fluid overload&#44; particularly when administered to fluid-unresponsive patients or when inappropriate resuscitation goals are pursued&#46; Unfortunately&#44; despite extensive research&#44; many uncertainties remain on the best perfusion monitoring and resuscitation target&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">The complexities of persistent hyperlactatemia</span><p id="par0010" class="elsevierStylePara elsevierViewall">Recent guidelines recommend lactate normalization as a resuscitation target&#46; However&#44; the rationale of lactate-guided therapy has been challenged as it may expose patients to the risk of over-resuscitation considering that the decrease in lactate levels over time is relatively slow even in survivors&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">2&#44;3</span></a> In addition&#44; lactate is a non-specific marker of hypoperfusion and several pathogenic mechanisms besides hypoperfusion may be involved&#46; Adrenergic-driven muscle glycolysis and impaired hepatic lactate clearance are important confounding mechanisms in septic shock&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#44;2</span></a> Recognizing a clinical pattern of hypoperfusion-related hyperlactatemia is important since optimizing systemic blood flow in that context could improve prognosis&#46; In contrast&#44; pursuing additional resuscitation in non-hypoperfusion-related cases might lead to the toxicity of over-resuscitation&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Multimodal perfusion monitoring including flow-sensitive parameters such as central venous O<span class="elsevierStyleInf">2</span> saturation &#40;ScvO<span class="elsevierStyleInf">2</span>&#41;&#44; central venous-arterial pCO<span class="elsevierStyleInf">2</span> gradient &#40;Pcv-aCO<span class="elsevierStyleInf">2</span>&#41;&#44; and peripheral perfusion&#44; may disclose the presence of hypoperfusion-related hyperlactatemia when any of these variables is abnormal&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1&#44;2&#44;4</span></a> Persistent hyperlactatemia without a hypoperfusion context is associated with a better prognosis&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> and eventually this condition could be managed more conservatively&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">The role of capillary refill time &#40;CRT&#41; assessment</span><p id="par0020" class="elsevierStylePara elsevierViewall">CRT emerges as a rational alternative to guide septic shock resuscitation&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> The skin territory lacks auto-regulatory flow control&#44; and therefore&#44; sympathetic activation impairs skin perfusion during circulatory dysfunction&#44; a phenomenon that can be evaluated by peripheral perfusion assessment&#46; Several studies confirm that abnormal peripheral perfusion after initial<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> or advanced<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> resuscitation is associated with increased morbidity and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">6&#44;7</span></a> The improved prognosis associated with CRT normalization&#44; its rapid-response time to fluid loading&#44; its relative simplicity&#44; its availability in resource-limited settings&#44; and its capacity to change in parallel with perfusion of physiologically relevant territories such as the hepatosplanchnic region&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> constitute strong reasons to consider CRT as target for initial septic shock resuscitation&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">The ANDROMEDA-SHOCK trial</span><p id="par0025" class="elsevierStylePara elsevierViewall">ANDROMEDA-SHOCK was a multicenter&#44; randomized controlled trial comparing CRT- versus lactate-targeted resuscitation in patients with early septic shock&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> The hypothesis was that targeting CRT assessed with a standardized method&#44; would lead to decreased mortality and organ dysfunction&#46; The protocol mandated sequential steps starting with fluid challenges&#44; followed by vasoactive-related interventions if necessary&#44; until the target was reached&#46; CRT-targeted resuscitation was associated with lower mortality &#40;34&#46;9&#37; vs&#46; 43&#46;4&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;06&#41;&#44; beneficial effects on organ dysfunction&#44; and less treatment intensity&#46; The worldwide impact and immediate application of CRT-guided resuscitation makes additional research an urgent task &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">The concept of hemodynamic coherence in septic shock</span><p id="par0030" class="elsevierStylePara elsevierViewall">Hemodynamic coherence is a condition in which resuscitation of systemic macrohemodynamic variables results in concurrent improvement in regional and microcirculatory blood flow&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">9&#8211;11</span></a>&#46; Impaired vascular tone with decreased venous return and arterial hypotension are key pathogenic mechanisms in early septic shock&#46; At this stage&#44; fluid resuscitation &#40;in fluid-responsive patients&#41; and mean arterial pressure &#40;MAP&#41; optimization may improve macrocirculatory&#44; regional&#44; and microcirculatory blood flow&#44; which is consistent with preserved hemodynamic coherence and associated with better prognosis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">At more advanced stages&#44; when excessive adrenergic tone and microvascular&#47;endothelial inflammation predominate&#44; regional flow distribution and microcirculatory dysfunction may not respond to systemic blood flow optimization&#46; Thus&#44; hemodynamic coherence is lost&#44; and efforts to further increase stroke volume or MAP by fluids or vasoactive agents might lead to fluid overload or catecholamine toxicity&#46; This could result in worsening tissue perfusion by promoting interstitial edema&#44; or by further deteriorating regional perfusion&#46; How to treat patients at this stage is uncertain and a matter of future research&#44; including the potential role of early immunomodulating therapies&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">CRT&#58; the link between macrocirculation and the microcirculation&#63;</span><p id="par0040" class="elsevierStylePara elsevierViewall">Capillary refill time &#40;CRT&#41; appears as a physiologically sound target and its improvement after stroke volume optimization is a signal of tissue reperfusion in patients with septic shock&#46; Some observations support the potential role of CRT in revealing the status of hemodynamic coherence&#46; First&#44; three recent studies show that patients with normal vs&#46; abnormal CRT after fluid resuscitation exhibit a highly significant difference in mortality &#40;ranging from 9 to 23&#37; vs&#46; 45 to 55&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">5&#8211;7</span></a> This remarkable and consistent difference suggests&#44; although does not prove&#44; a preserved hemodynamic coherence in CRT normalizers &#40;responders&#41;&#46; Second&#44; improvement in CRT after fluid resuscitation is associated with a parallel increase in hepatosplanchnic blood flow&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> Third&#44; CRT showed the fastest kinetics of recovery in septic shock survivors as compared with other commonly used perfusion parameters&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Fourth&#44; normalization of CRT in the ANDROMEDA-shock study was associated with less organ dysfunction&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">On the other hand&#44; an abnormal CRT not responding to increments in systemic flow might be explained by several mechanisms including a more advanced stage of septic shock with uncoupling or loss of hemodynamic coherence&#59; an excessive adrenergic tone with regional hypoperfusion&#59; or a more severe systemic inflammatory state with endothelial&#47;coagulation activation&#47;dysfunction which could lead to impairment and heterogeneity of microcirculatory flow&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> None of these mechanisms may respond to systemic flow optimization at this stage&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Based on the preceding considerations&#44; we could propose that CRT response to a rapid flow increasing maneuver may be used as a novel &#8220;hemodynamic coherence test&#46;&#8221; A parallel improvement in regional blood flow&#44; microcirculation and hypoperfusion-related parameters should be expected in patients that normalize CRT&#44; as reflection of preserved hemodynamic coherence&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusions</span><p id="par0055" class="elsevierStylePara elsevierViewall">Multimodal perfusion monitoring might be useful to determine a hypoperfusion-context in persistent hyperlactatemia&#44; thus promoting a physiologically-oriented septic shock resuscitation&#46; CRT-guided septic shock resuscitation is associated with decreased mortality and organ dysfunction&#46; CRT changes after rapid flow increasing maneuvers may identify the status of hemodynamic coherence&#44; helping clinicians to decide on the most appropriate strategy for each stage&#46; Further research is required to test these hypotheses&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflict of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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                  \t\t\t\t"><span class="elsevierStyleItalic">Main findings of the ANDROMEDA-SHOCK study favoring CRT-targeted septic shock resuscitation</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lower mortality &#40;34&#46;9&#37; vs&#46; 43&#46;4&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;06&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Less organ dysfunctions at 72<span class="elsevierStyleHsp" style=""></span>h &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;045&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Lower mortality in the predefined subgroup of patients with less organ dysfunctions at baseline &#40;20&#46;4&#37; vs&#46; 39&#46;3&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Faster improvement in organ dysfunctions during the first 72<span class="elsevierStyleHsp" style=""></span>h &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Less resuscitation fluids &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Less vasopressor testing &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Some unsolved issues and challenges for a CRT-focused research agenda</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Mechanisms of the beneficial effect of CRT-targeted resuscitation in the ANDROMEDA-SHOCK study&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Pathophysiologic determinants of an abnormal CRT&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Does CRT accurately represent skin blood flow&#63;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Is CRT an equivalent of a vascular occlusion test to detect abnormal microvascular reactivity&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Is there a relationship between an abnormal CRT and adrenergic tone&#63;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Does CRT respond in real-time to increments in systemic blood flow&#63;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>What is the impact of vasoactive agents on CRT&#63;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Does normalization of CRT after a fluid challenge predict the status of hemodynamic coherence between macrocirculation and regional&#47;microcirculatory blood flow&#63;&nbsp;\t\t\t\t\t\t\n
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Article information
ISSN: 21735727
Original language: English
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Idiomas
Medicina Intensiva (English Edition)